Breaking barriers in lung research with engineered airway epithelial cell culture models

The airway epithelium is a key regulator of immune responses, tissue repair, and airway remodeling in chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review evaluates engineered in vitro airway epithelial models and their value to investigate disease mechanisms, drug responses, and epithelial-mesenchymal transitions (EMT).

Recent studies demonstrated that different in vitro models can replicate disease-specific features, including goblet cell metaplasia, epithelial barrier disruption, and EMT, providing mechanistic insight as well as drug screening tools in asthma, COPD, and IPF. Airway epithelial cells (AEC) cultured in air-liquid interface (ALI) allow robust epithelial differentiation to perform functional and barrier integrity studies. Lung organoids provide organ-like structures that capture complex epithelial-mesenchymal crosstalk. Lung-on-chip (LoC) platforms integrate mechanical forces, dynamic airflow, and microfluidics to recapitulate in-vivo microenvironments. Each model presents specific strengths and weaknesses, making careful selection essential.

The strategic selection and integration of engineered airway epithelial models improves mechanistic understanding, supports preclinical drug evaluation, and reduces reliance on animal experiments. These platforms provide physiologically relevant, patient-specific systems for the advancement of translational lung research.